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PubMed1997

Describing the natural heterogeneity of aging using multilevel regression models.

Aging has been defined as the process of change that occurs in the individual during the course of time following the early stages of growth and development. While this process occurs in everyone, it varies from person to person. Longitudinal studies have emerged as the only method to study individual change directly and to identify factors associated with that change. Multilevel or mixed-effects regression models have proven to be a useful tool for describing the natural heterogeneity that occurs in studies of aging. These models, along with recent developments in estimation procedures and numerical techniques, have made it possible to estimate in a unified analysis the average rates of change for the study population, as well as individual deviations from these average rates. One type of multilevel models, mixed-effects models, assumes that the correlation among longitudinal measurements for an individual is due to some latent characteristics that give the individual an initial level or rate of change which is higher or lower than average. This paper discusses the application of mixed-effects models using random effects for the estimation of individual differences to aspects of human aging which have been observed over the first 35 years of the ongoing Baltimore Longitudinal Study of Aging.

Adult↗
PubMed1995

Violence by male partners against women during the childbearing year: a contextual analysis.

OBJECTIVES: Many contextual analyses that bridge the micro-level-macro-level gap in identifying risk factors for adverse outcomes have not used methods appropriate for multilevel data. The purpose of this paper is to illustrate the application of appropriate multi-level analytic methods and discuss their implications for public health. METHODS: A previously published individual-level model of physical violence perpetrated by male partners during the childbearing year was reanalyzed to include variables describing the neighborhoods where the women resided. Logistic regression with estimation methods of the generalized estimating equation was used for the contextual analysis. To assess the advantages of the generalized estimating equation over conventional logistic regression, both were used for the two-level model. RESULTS: The regression coefficients from the contextual model differed from the betas obtained in the individual-level model. Not only were neighborhood-level variables related to the risk of partner-perpetrated violence, but the presence of these macro-level variables in the models modified the relationships of the individual-level variables to the risk of violence. CONCLUSIONS: Two-level models that include individual- and community-level factors may be beneficial for purposes of explanation in public health research.

Adolescent↗
PubMed1998

[Complex injuries of the spine].

3 different types of complex spinal trauma are defined: Type I means a multilevel contiguous or non contiguous unstable injury, type II is described as a spinal injury with concomitant thoracic or abdominal lesion, type III stands for the coincidence of spinal injury and polytrauma. Overlapping of different types occurs. Type I: The incidence amounts according a german multicenter study to about 2.5%. Multilevel injuries need to be stabilized for a long distance from posterior. With a thorough analysis the segments to be fused are determined. Type II: The leading thoracic injury is a lung contusion which occurs in up to 50% of the cases. A CT scan of the thorax during the first diagnostic screening is recommended. Early reduction and stabilization from posterior should be aimed at. During the first two weeks anterior procedures are contraindicated. Abdominal injuries are to be found in 3-4% of all spinal injuries. All organs could be affected. A typical constallation is the "seat-belt syndrome" with lesions of the upper abdominal organs and a flexiondistraction injury of the upper lumbar spine. The main problem is to make the diagnosis of both components initially. Most of the patients may be treated in one operation by first taking care of the abdominal injury and than stabilizing the spine. The prognosis of this combination is favorable. Type III: In 17-18% of all polytraumatized patients lesions of the spine are to be diagnosed. From these only one third need surgical care. From 680 patients with operatively treated fractures of the thoracolumbar junction 6.2% were polytraumatized according to the multicenter study mentioned above. The risk of missing a spinal injury in polytrauma totals approximately 20%. Surgical stabilization should be performed in the primary phase (day-1-surgery). Additional injuries, potentially time consuming operations with a high blood loss sometimes necessitate a different approach. Non stabilized spinal injuries apparently do not have the same negative effect on the whole organism as long bone fractures. In the early phase of treatment on the C-spine only anterior procedures and on the thoracolumbar spine only posterior techniques should be applied.

Adolescent↗
PubMed2005

Contemporaneous relationship between substance abuse treatment and poly-substance use: evidence from the Persistent Effect of Treatment Studies.

Data from the Persistent Effect of Treatment Studies (PETS) are used to explore the relationship between duration of substance use treatment and simultaneous poly-substance using behaviors. Studying such contemporaneous relationships is especially important given the chronic nature of the substance-using population (McLellan, 2002) in the PETS study. Data were collected at intake to treatment programs and follow-up interviews were performed periodically at treatment program sites. One of the features of the analysis was the development of a poly-substance scale to measure multiple substance use. Multilevel models were implemented to examine the relationship between three levels of care (i.e., intensive outpatient, outpatient, and residential) and simultaneous poly-substance use. Contemporaneous effects of treatment were obtained such that higher duration of treatment was associated with drops in substance-using behaviors. This result supports the need for sustaining treatment for a population of chronic substance abusers.

Adult↗
PubMed1999

Cosmetic enhancement associated with surgery for obstructive sleep apnea.

OBJECTIVE: To document the capacity of surgery for obstructive sleep apnea (OSA) to incorporate techniques that incidentally improve the cosmetic features of the patients. STUDY DESIGN: Retrospective analysis of surgical outcomes at an academic practice. METHODS: Moderate to severe OSA usually requires multilevel pharyngeal surgery, including tongue base surgery. The surgical procedures, including hyoid myotomy and mandibular osteotomy with tongue advancement, afford the opportunity to address cosmetic deficits, such as microgenia and excessive submental skin and fat. Outcomes achieved using these procedures over a 4-year period were analyzed. RESULTS: Of 428 consecutive patients presenting for evaluation of sleep-related breathing disorders, 212 were deemed surgical candidates. Ninety-seven of these had office-based procedures for snoring, upper airway resistance syndrome, or mild OSA. The remaining 115 had formal surgical procedures done, and 68 of these had multilevel pharyngeal surgery. Of these, 12 had defined cosmetic deficiencies that were addressed at the time of the sleep apnea surgery. There were 7 men and 5 women, with a mean age of 48.2 years. The group was moderately obese (mean BMI = 31.8) and had moderate to severe OSA (mean RDI = 37.0, mean LSAT = 78%). Cosmetic deficits identified included turkey gobbler deformity (n = 8), microgenia (n = 6), excessive submental fat (n = 2), and nasal deformity (n = 1); several patients had more than one addressable problem. All patients achieved an improved postoperative appearance. Representative photographs are presented. CONCLUSIONS: A surgical approach to the management of sleep apnea affords an opportunity to also address cosmetic deficiencies, including excessive submental skin and fat, microgenia, and nasal deformities.

Cosmetic Techniques↗
PubMed2005

Sentinel nodes are identifiable in formalin-fixed specimens after surgeon-performed ex vivo sentinel lymph node mapping in colorectal cancer.

BACKGROUND: In recent years, the technique of sentinel lymph node (SLN) mapping has been applied to colorectal cancer. One aim was to ultrastage patients who were deemed node negative by routine pathologic processing but who went on to develop systemic disease. Such a group may benefit from adjuvant chemotherapy. METHODS: With fully informed consent and ethical approval, 37 patients with primary colorectal cancer and 3 patients with large adenomas were prospectively mapped. Isosulfan blue dye (1 to 2 mL) was injected around tumors within 5 to 10 minutes of resection. After gentle massage to recreate in vivo lymph flow, specimens were placed directly into formalin. During routine pathologic analysis, all nodes were bivalved, and blue-staining nodes were noted. These later underwent multilevel step sectioning with hematoxylin and eosin and cytokeratin staining. RESULTS: SLNs were found in 39 of 40 patients (98% sensitivity), with an average of 4.1 SLNs per patient (range, 1-8). In 14 of 16 (88% specificity) patients with nodal metastases on routine reporting, SLN status was in accordance. Focused examination of SLNs identified occult tumor deposits in 6 (29%) of 21 node-negative patients. No metastatic cells were found in SLNs draining the three adenomas. CONCLUSIONS: The ability to identify SLNs after formalin fixation increases the ease and applicability of SLN mapping in colorectal cancer. Furthermore, the sensitivity and specificity of this simple ex vivo method for establishing regional lymph node status were directly comparable to those in previously published reports.

Adenoma↗
PubMed2002

Healing of autologous bone in a titanium mesh cage used in anterior column reconstruction after total spondylectomy.

STUDY DESIGN: Autologous bone inside a titanium mesh cage, used as an anterior strut in a reconstruction after total spondylectomy, was histologically examined in a postmortem specimen. OBJECTIVES: To determine whether the autologous bone inside the titanium mesh cage attained fusion and remodeling in a combined reconstruction, consisting of an anterior titanium mesh cage with posterior multilevel instrumentation, after total spondylectomy. SUMMARY OF BACKGROUND DATA: There are few previous reports on the histologic analysis of the bone inside a titanium mesh cage when it is used clinically as an anterior column support in a spinal fusion. Attaining biologic bony fusion is desirable for long-term stability after total spondylectomy. METHODS: A postmortem specimen from a 16-year-old boy with Ewing's sarcoma at T6, who died of lung metastasis 16 months after total spondylectomy and combined reconstruction, was analyzed. RESULTS: Histologic examination revealed many viable cells and normal lamella of trabecular bone formation in the grafted bone inside the mesh. Consecutive trabecular cancellous bony fusion between the grafted bone and the adjacent vertebral bodies was achieved. CONCLUSION: Remodeling and fusion of the grafted bone inside the titanium mesh cage was observed. Combined reconstruction using an anterior titanium mesh cage with posterior multilevel instrumentation after total spondylectomy makes it possible to achieve biologic fusion of the bone inside the mesh cage with the adjacent vertebral bodies.

Adolescent↗
PubMed2006

Household and community socioeconomic and environmental determinants of child nutritional status in Cameroon.

BACKGROUND: Undernutrition is a leading cause of child mortality in developing countries, especially in sub-Saharan Africa. We examine the household and community level socioeconomic and environmental factors associated with child nutritional status in Cameroon, and changes in the effects of these factors during the 1990s economic crisis. We further consider age-specific effects of household economic status on child nutrition. METHODS: Child nutritional status was measured by weight-for-age (WAZ) and height-for-age (HAZ) z-scores. Data were from Demographic and Health Surveys conducted in 1991 and 1998. We used analysis of variance to assess the bivariate association between the explanatory factors and nutritional status. Multivariate, multilevel analyses were undertaken to estimate the net effects of both household and community factors. RESULTS: Average WAZ and HAZ declined respectively from -0.70 standard deviations (SD), i.e. 0.70 SD below the reference median, to -0.83 SD (p = 0.006) and from -1.03 SD to -1.14 SD (p = 0.026) between 1991 and 1998. These declines occurred mostly among boys, children over 12 months of age, and those of low socioeconomic status. Maternal education and maternal health seeking behavior were associated with better child nutrition. Household economic status had an overall positive effect that increased during the crisis, but it had little effect in children under 6 months of age. Improved household (water, sanitation and cooking fuel) and community environment had positive effects. Children living in the driest regions of the country were consistently worst off, and those in the largest cities were best off. CONCLUSION: Both household and community factors have significant impact on child health in Cameroon. Understanding these relationships can facilitate design of age- and community-specific intervention programs.

Adolescent↗
PubMed2004

Simplified kinetic analysis of tumor 18F-FDG uptake: a dynamic approach.

UNLABELLED: Standardized uptake value (SUV) is often used to quantify (18)F-FDG tumor use. Although useful, SUV suffers from known quantitative inaccuracies. Simplified kinetic analysis (SKA) methods have been proposed to overcome the shortcomings of SUV. Most SKA methods rely on a single time point (SKA-S), not on tumor uptake rate. We describe a hybrid between Patlak analysis and existing SKA-S methods, using multiple time points (SKA-M) but reduced imaging time and without measurement of an input function. We compared SKA-M with a published SKA-S method and with Patlak analysis. METHODS: Twenty-seven dynamic (18)F-FDG scans were performed on 11 cancer patients. A population-based (18)F-FDG input function was generated from an independent patient population. SKA-M was calculated using this population input function and either a short, late, dynamic acquisition over the tumor (starting 25-35 min after injection and ending approximately 55 min after injection) or dynamic imaging 10 or 25 min to approximately 55 min after injection but using only every second or third time point, to permit a 2- or 3-field-of-view study. SKA-S was also calculated. Both SKA-M and SKA-S were compared with the gold standard, Patlak analysis. RESULTS: Both SKA-M (1 field of view) and SKA-S correlated well with Patlak slope (r > 0.99, P < 0.001, and r = 0.96, P < 0.001, respectively), as did multilevel SKA-M (r > 0.99 and P < 0.001 for both). Mean values of SKA-M (25-min start time) and SKA-S were statistically different from Patlak analysis (P < 0.001 and P < 0.04, respectively). One-level SKA-M differed from the Patlak influx constant by only -1.0% +/- 1.4%, whereas SKA-S differed by 15.1% +/- 3.9%. With 1-level SKA-M, only 2 of 27 studies differed from K(i) by more than 20%, whereas with SKA-S, 10 of 27 studies differed by more than 20% from K(i). CONCLUSION: Both SKA-M and SKA-S compared well with Patlak analysis. SKA-M (1 or multiple levels) had lower variability and bias than did SKA-S, compared with Patlak analysis. SKA-M may be preferred over SUV or SKA-S when a large unmetabolized (18)F-FDG fraction is expected and 1-3 fields of view are sufficient.

Breast Neoplasms↗
PubMed2002

Multilevel likelihood ratios for identifying exudative pleural effusions(*).

STUDY OBJECTIVES: To determine multilevel likelihood ratios for pleural fluid tests that are commonly used to discriminate between exudative and transudative pleural effusions. DESIGN: Meta-analysis of patient-level data. PATIENT DATA: Selected studies included patients with diagnoses of exudative or transudative pleural effusions who underwent thoracentesis and laboratory analysis of their pleural fluid. MEASUREMENTS AND METHODS: Studies were identified by searching MEDLINE and related bibliographies. Data were obtained for 1,448 patients from seven primary investigators or extracted from dot plots in published reports. Likelihood ratios were calculated from extracted data stratified across ranges of test result values. RESULTS: Sufficient data were available to calculate multilevel likelihood ratios for the elements of Light's criteria (pleural fluid lactate dehydrogenase [LDH], ratio of pleural fluid to serum LDH, and ratio of pleural fluid to serum protein), pleural fluid protein, ratio of pleural fluid to serum cholesterol, pleural fluid cholesterol, and gradient of pleural fluid to serum albumin. Each of these tests provided levels of likelihood ratios through the most clinically relevant range (0 to 10). CONCLUSION: Multilevel likelihood ratios combined with a clinician's estimation of the pretest probability of an exudative effusion improve the diagnostic accuracy of discriminating between exudative and transudative pleural effusions. Likelihood ratios avoid the use of confusing terms, such as "pseudoexudates," that derive from the use of single cutoff points for pleural fluid tests.

Diagnosis, Differential↗
PubMed2002

Role of the tongue base suspension suture with The Repose System bone screw in the multilevel surgical management of obstructive sleep apnea.

OBJECTIVE: The Repose System (tongue base suspension) is a new, minimally invasive technique for tongue base suspension in the treatment of obstructive sleep apnea. The purpose of this project was to describe our preliminary experience using this tongue base suspension system in conjunction with uvulopalatopharyngoplasty (UPPP) in the multilevel surgical approach to the management of obstructive sleep apnea (OSA). STUDY DESIGN: We conducted a retrospective analysis of 19 consecutive patients undergoing UPPP and The Repose System tongue base suspension for the management of obstructive sleep apnea during a 1-year period (1998 through 1999). RESULTS: Fifteen patients (11 men and 4 women) had complete preoperative and postoperative polysomnographic data. A 46% reduction in the preoperative respiratory disturbance index (RDI) (38.7 +/- 12.3) versus the postoperative RDI (21.0 +/- 7.4, P < 0.05) was demonstrated at a mean of 3.8 months after surgery. The apnea index demonstrated a 39% reduction. The surgical cure rate was 20% (3 of 15 patients). CONCLUSIONS: The Repose System in conjunction with UPPP has been shown to produce significant reductions in the RDI and apnea index as well as a significant increase in O2 saturation. Despite the improvement in these objective parameters, the overall surgical cure rate was only 20% (3 of 15 patients) in this retrospective series. Further research is warranted to define the role of The Repose System in the management of obstructive sleep apnea patients with multilevel airway obstruction.

Bone Screws↗
PubMed2006

The combined effect of lower-limb multilevel botulinum toxin type a and comprehensive rehabilitation on mobility in children with cerebral palsy: a randomized clinical trial.

OBJECTIVE: To evaluate the combined effect on mobility of treatment with multilevel botulinum toxin type A (BTX-A) and comprehensive rehabilitation in children with cerebral palsy (CP). DESIGN: Randomized clinical trial using a multiple baseline design. The intervention group was treated 6 weeks after randomization. The control group was treated after a longer period of 18 to 30 weeks. Repeated measurements in both groups were continued throughout the process, before and up to 48 weeks after treatment. SETTING: Four departments of rehabilitation medicine in The Netherlands. PARTICIPANTS: Forty-six children with spastic CP (mean age +/- standard deviation, 8.0+/-2.1y). INTERVENTION: The intervention group (n=23) was treated with multilevel BTX-A and comprehensive rehabilitation. Control group subjects (n=23) continued with their usual physical therapy (PT) for 18 to 30 weeks, and then also received multilevel BTX-A and comprehensive rehabilitation. MAIN OUTCOME MEASURES: The primary outcome measure was the Gross Motor Function Measure (GMFM-66); the secondary measures were problem score and energy cost. RESULTS: The treatment effect during the first 24 weeks of follow-up in the intervention group was compared with the effect of usual PT in the control group. Treatment with multilevel BTX-A and comprehensive rehabilitation provided a significantly greater improvement at 12 and 24 weeks in both the GMFM-66 (2.1 points, P=.02; and 3.5 points, P<.01, respectively) and problem score (1.8 and 1.7 points, P<.001, respectively) compared with usual PT. No difference was found in energy cost. Before-after analysis of the total group (n=46) showed a significant long-term improvement (48wk) on all outcome measures. CONCLUSIONS: Treatment with multilevel BTX-A and comprehensive rehabilitation significantly improves mobility as measured by the GMFM-66 and problem score in children with CP.

Botulinum Toxins, Type A↗
PubMed2006

Measures of familial aggregation depend on definition of family history: meta-analysis for colorectal cancer.

OBJECTIVE: Familial aggregation, a primary theme in genetic epidemiology, can be estimated from family studies based on an index person. The excess risk due to the presence of affected family members can be classified according to whether disease in the relatives is considered a risk factor for the index person (type I relative risk) or whether the disease status of the index person is considered a risk factor for the relatives (type II relative risk). STUDY DESIGN AND SETTING: A meta-analysis of published colorectal cancer studies reporting a measure of familial association was performed and application of multilevel linear regression to model age-specific relative risks presented. RESULTS: The pooled type I relative risk of colorectal cancer given any affected first-degree relative (based on 20 studies) was 2.26 (95% confidence interval CI = 1.86, 2.73) and decreased with the age of the consultand. The pooled type II estimate (based on seven studies) was 2.81 (95% CI = 2.05, 3.85). CONCLUSION: Type I relative risks are useful in clinical counseling settings when a consultand wants to know his/her disease risk given his or her family history. Type II relative risks can be used to quantify the risk of disease to relatives of an affected individual and then identify subjects eligible for screening.

Age of Onset↗
PubMed1999

Analysing repeated measurements data: a practical comparison of methods.

A variety of methods are available for analysing repeated measurements data where the outcome is continuous. However, there is little information on how established methods, such as summary statistics and repeated measures analysis of variance (RMAOV), compare in practice with methods that have become available to applied statisticians more recently, such as marginal models (based on generalized estimating equation methodology) and multilevel models (that is, hierarchical random effects models). The aim of this paper is to exemplify the use of these methods, and directly compare their results by application to a clinical trial data set. The focus is on practical aspects rather than technical issues. The data considered were taken from a clinical trial of treatments for asthma in 240 children, in which a baseline and four post-randomization measurements of outcomes were taken. The simplicity of the method of summary statistics using the post-randomization mean of observations provided a useful initial analysis. However, fixed time effects or treatment-time interactions cannot be included in such an analysis, and choice of appropriate weighting when there is substantial missing data is problematic. RMAOV, marginal models and multilevel models generally provided similar estimates and standard errors for the treatment effects, although in one example with a relatively complex variance structure the marginal model produced less efficient estimates. Two advantages of multilevel models are that they provide direct estimates of variance components which are often of interest in their own right, and that they can be naturally extended to handle multivariate outcomes.

Adolescent↗
PubMed2002

Moment evolution and level-crossing statistics in dichotomous and multilevel flows with time-dependent control parameters.

We study the dynamics of the first two moments and of threshold crossings by the stochastic trajectory in dichotomous diffusion x=xi(t), where xi(t) is a dichotomous Markov process. The transition rate of the latter is regarded as a control parameter and allowed to have specified time variations. The stabilizing or destabilizing effect of this variation is demonstrated, and qualitative changes in the statistical properties of the system are shown to occur. The analysis is then extended to linear dichotomous flow, and to a generalization of dichotomous diffusion in which x is driven by a multilevel Markov noise.

Journal Article↗
PubMed2006

Discussing patient management online: the impact of roles on knowledge construction for students interning at the paediatric ward.

The objectives of this study are to explore the use of asynchronous discussion groups during medical students' clinical rotation in paediatrics. In particular, the impact of role assignment on the level of knowledge construction through social negotiation is studied. Case-based asynchronous discussion groups were introduced to enhance reflection and critical thinking on patient management and treatment, and to offer an exercise in evidence-based medical practice. Groups of approximately 4-5 students were asked to discuss 4 authentic cases during clinical rotation in paediatrics. 49 students interning at the paediatric ward participated in this study. With respect to role assignment, differences between groups (1) with a student or an instructor as moderator and (2) with or without a developer of alternatives for patient management were explored. A content analysis was performed to explore the different levels of social construction of knowledge. The results of multilevel logit analyses show a significant difference in knowledge construction through social negotiation between conditions with a student moderator and conditions where the instructor is moderating, but only when a developer of alternatives is involved. No significant difference was revealed between student-moderated and instructor-moderator groups without a developer of alternatives. It can be concluded that when both the moderator and developer role are assigned to students, their contributions are more likely to reflect a high level of knowledge construction.

Adult↗
PubMed1999

Multisegmental cervical spondylotic myelopathy and radiculopathy treated by multilevel oblique corpectomies without fusion.

OBJECTIVE: The description of the technique of multilevel oblique corpectomy (MOC) without fusion in the treatment of spondylotic myelopathy and radiculopathy and the analysis of the results of this technique from a series of 101 cases are presented. METHODS: MOC is performed using an anterolateral approach with control of the vertebral artery. The vertebral bodies are drilled obliquely from the lateral side toward the opposite posterolateral corner. More than half of the vertebral bodies are preserved, and no fusion procedure is required. The series of patients from 1992 through 1997 included 54 men and 47 women, with an average age of 57.9 years, who presented with myelopathy (n = 66) or radiculopathy (n = 35). MOC was realized on one to five levels from C2-C3 to C7-T1. Follow-up data were obtained by performing dynamic roentgenography, computed tomography, and magnetic resonance imaging 2 months, 1 year, and 3 years after surgery. RESULTS: The results (Japanese Orthopedic Association score) were improvement in 82% of the patients, worsening in 8%, and stabilization in 10%. Better results were observed in younger patients (<50 yr). No relation between results and duration of symptoms or number of levels could be established. One death occurred as a result of multiorgan failure. No late deterioration was observed; however, three patients with particular features showed delayed instability requiring fusion. CONCLUSION: MOC is a safe and efficient technique. It must be applied for patients with anterior compression and straight or kyphotic axis of the spine. No fusion is required regardless of the number of levels, providing there are no soft discs and there is no preoperative instability.

Bone Transplantation↗
PubMed2000

When should epidemiologic regressions use random coefficients?

Regression models with random coefficients arise naturally in both frequentist and Bayesian approaches to estimation problems. They are becoming widely available in standard computer packages under the headings of generalized linear mixed models, hierarchical models, and multilevel models. I here argue that such models offer a more scientifically defensible framework for epidemiologic analysis than the fixed-effects models now prevalent in epidemiology. The argument invokes an antiparsimony principle attributed to L. J. Savage, which is that models should be rich enough to reflect the complexity of the relations under study. It also invokes the countervailing principle that you cannot estimate anything if you try to estimate everything (often used to justify parsimony). Regression with random coefficients offers a rational compromise between these principles as well as an alternative to analyses based on standard variable-selection algorithms and their attendant distortion of uncertainty assessments. These points are illustrated with an analysis of data on diet, nutrition, and breast cancer.

Breast Neoplasms↗